Porphyrin-polyamine conjugates for cancer therapy

• US 20040152687A1
• Filed: 06/24/2003
• Published: 08/05/2004
• Est. Priority Date: 06/26/2002
• Status: Active Grant

• Current Assignee: Cellgate, Inc. (Tbg Diagnostics Limited)
• Original Assignee: Cellgate, Inc. (Tbg Diagnostics Limited)
• Inventors: Wang, Yu, Basu, Hirak S., Valasinas, Aldonia L., Blokhin, Andrei V., Sarkar, Aparajita, Reddy, Venodhar K., Frydman, Benjamin, Marton, Laurence J., Bhattacharya, Subhra
• Granted Patent: US 7,026,347 B2
• Time in Patent Office: Days
• US Class Current: 514/185
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 487/22 in which the condensed system contains four or more hetero rings

Abstract

Porphyrin-polyamine conjugate compounds are disclosed which have anticancer and antitumor effects. The porphyrin moiety selectively localizes in tumors, while the polyamine moiety serves as a cytotoxic agent. Methods of making and using the porphyrin-polyamine conjugate compounds are also disclosed.

Claims

1. A composition comprising a compound according to the formula

16. The composition of claim 1, wherein each —

K is independently Q;

where each Q is independently selected from the group consisting of

wherein only one D moiety is selected from the group consisting of C₁-C₃₂ alkyl and all remaining D moieties are H;

wherein three P groups are selected from the group consisting of —

H and —

CH₃;

wherein the fourth P group is absent and the Q moiety is attached to the remainder of the molecule at that valence; and

wherein y is 2, 3,or 4 and z is 0, 1, or 2.

19. The composition of claim 1, wherein —

K is

2. A composition comprising a compound according to the formula

3. The composition of claim 2, where G is independently selected from —

(C═

O)—

N(P)— and

—

N(P)—

(C═

O)—

.

4. The composition of claim 2, where the Q moiety is attached to the remainder of the molecule at any N atom in the Q moiety by removing a P substituent of the Q moiety to form an open valence for attachment to the remainder of the molecule.

5. The composition of claim 2, wherein each A and B substituent, if present, is selected from C₁-C₁₂ alkyl.

6. The composition of claim 2, wherein at least one A substituent comprises a cyclopropane group.

7. The composition of claim 2 comprising a compound of the formula

8. The composition of claim 7, where J₁ and J₂ are independently M and each M is independently selected from the group consisting of —

(B-A-B)-G-(B-A-B)—

(N(P)—

B-A-B)_n—

K.

9. The composition of claim 8, wherein at least one B-A-B unit comprises a cycloalkyl moiety.

10. The composition of claim 9, wherein at least one B-A-B unit comprises a cyclopropyl moiety.

11. The composition of claim 7, where J₁ and J₂ are independently M and each M is independently selected from the group consisting of —

C₁-C₁₂ alkyl-G-C₁-C₁₂ alkyl-(N(P)—

B-A-B)_n—

K.

12. The composition of claim 7, where J₁ and J₂ are independently M and each M is independently selected from the group consisting of —

C₁-C₁₂alkyl-(C═

O)—

N(P)—

C₁-C₁₂ alkyl-(N(P)—

B-A-B)_n—

K.

13. The composition of claim 7, where J₁ and J₂ are independently M and each M is independently selected from the group consisting of —

(CH₂)₂C(═

O)N(P₂)—

C₁-C₄ alkyl-[NH(CH₂CH₂CH₂CH₂)]_fC₁-C₁₂ alkyl, where P₂ is H, methyl, or ethyl, and f is an integer from 1 to 10.

14. The composition of claim 10, where J₁ and J₂ are identical.

15. The composition of claim 11, where J₁ and J₂ are identical.

17. The composition of claim 2, wherein each —

K is independently Q;

where each Q is independently selected from the group consisting of

wherein only one D moiety is selected from the group consisting of C₁-C₃₂ alkyl and all remaining D moieties are H;

wherein three P groups are selected from the group consisting of —

H and —

CH₃;

wherein the fourth P group is absent and the Q moiety is attached to the remainder of the molecule at that valence; and

wherein y is 2, 3, or 4 and z is 0, 1, or 2.

18. The composition of claim 6, wherein each —

K is independently Q;

where each Q is independently selected from the group consisting of

wherein only one D moiety is selected from the group consisting of C₁-C₃₂ alkyl and all remaining D moieties are H;

wherein three P groups are selected from the group consisting of —

H and —

CH₃;

wherein the fourth P group is absent and the Q moiety is attached to the remainder of the molecule at that valence; and

wherein y is 2, 3, or 4 and z is 0, 1, or 2.

20. The composition of claim 2, wherein —

K is